Project Summary Electrical impedance spectroscopy (EIS) is a sensitive label-free technique that has proved to be a powerful tool for a wide range of live cell studies. Measurement of the local impedance of live cells on an entire surface is highly desired, but so far has not been possible with current EIS technology. This project aims at the development of a new microscopy that can capture high-resolution impedance images of live cells. The proposed new microscopy is based on principles that are completely different from the conventional EIS. Instead of measuring impedance electrically, it images the local impedance of the entire surface optically with sub-micron spatial resolution. This simplifies the impedance measurement without sacrificing sensitivity and, more importantly, it introduces new exciting capabilities including: 1) sensor chips can be easily fabricated and prepared for cell attachment;2) the entire sensor chip or selected region of interest can be analyzed for detailed studies, which is important because it enables the tracking of individual cells or even region within single cells with the best sensitivity and spatial resolution;3) conventional surface plasmon resonance images can be obtained simultaneously, which provide detailed information on cell/substrate interaction;and 4) the instrument will be built based on a conventional inverted optical microscope, so that in-situ phase contrast and fluorescence microscopy images can be obtained for the same sample if desired. The project includes the following four tasks: 1) build a high-resolution optical impedance microscope system;2) establish data acquisition, processing, and analysis algorithms for live cell analysis;3) study the relationships between impedance microscopy images and cell adhesion behavior;and 4) test and evaluate the optical impedance microscope for additional studies of cells including wound healing, toxicology and motility. PUBLIC HEALTH RELEVANCE (provided by applicant): This project aims at the development of a new label-free microscopy that can capture sub-micron resolution impedance images of live cells optically. In addition, conventional surface plasmon resonance, optical and fluorescence microscopy images can be obtained simultaneously. The success of this project will provide a new tool that has a broad range of applications on cell dynamic studies.